EP2207900A1 - Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis - Google Patents
Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesisInfo
- Publication number
- EP2207900A1 EP2207900A1 EP08839081A EP08839081A EP2207900A1 EP 2207900 A1 EP2207900 A1 EP 2207900A1 EP 08839081 A EP08839081 A EP 08839081A EP 08839081 A EP08839081 A EP 08839081A EP 2207900 A1 EP2207900 A1 EP 2207900A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- nucleic acid
- dntp
- fluorophore
- consecutive nucleotide
- analogues
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/14—Pyrrolo-pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
- C12Q2525/30—Oligonucleotides characterised by their secondary structure
- C12Q2525/301—Hairpin oligonucleotides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2537/00—Reactions characterised by the reaction format or use of a specific feature
- C12Q2537/10—Reactions characterised by the reaction format or use of a specific feature the purpose or use of
- C12Q2537/157—A reaction step characterised by the number of molecules incorporated or released
Definitions
- a method for determining the identity of each of a series of consecutive nucleotide residues in a self- priming nucleic acid comprising: a) contacting the self-priming nucleic acid with (i) at least four different deoxynucleotide triphosphate (dNTP) analogues, each having the structure : wherein F is a fluorophore, b is a base which is adenine, guanine, cytosine, uracil or thymine, wherein the fluorophore attached through a linker to each type of base differs in its emission or excitation spectra from a fluorophore attached to each of the remaining types of bases, and each of the four dNTP analogues differs from the remaining three dNTP analogues by having a different base, and wherein L is a cleavable linker molecule comprising the structure:
- a method for increasing a read length of DNA sequencing by synthesis coupled with Sanger dideoxynucleotide terminating reaction (a) providing deoxynucleotide triphosphate analogues wherein the deoxynucleotide triphosphate analogues differ from deoxynucleotide triphosphates by having a methylazido group attached to a 3' 0 atom thereof and providing dideoxynucleotide triphosphate analogues wherein the dideoxynucleotide triphosphate analogues differ from dideoxynucleotide triphosphates by having a detectable marker attached to a 1 nitrogen or a 9 nitrogen of a base thereof through a linker comprising the structure
- ⁇ represents a point of attachment to the first portion and ⁇ represents a point of attachment to the third portion .
- a linker is cleaved by contacting the linker with tris (2-carboxyethyl) phosphine .
- one or more linkers are photocleavable or chemically cleavable.
- the DNA sequence is reset by reattaching the original primer, extending the chain with natural or minimally modified nucleotides to the end of the first round sequence, and then sequencing from that point.
- the second strategy relies on annealing of a second round primer that is longer than the first, containing at its 5' end the same sequence as the original primer, followed by a run of 20 universal nucleotides such as inosine, from which the second round of sequencing can be primed.
- deoxyribonucleotides diphosphate can also play such role, replacing the 3' -O-Ri- dNTPs, during enzymatic incorporation (Fig. 30) .
- the 3'-0H is also restored after the cleavage step so that the next stage of SBS can be carried out. Therefore, it is possible to recover all the DNA templates after each round of sequencing, dramatically increasing the potential read-length of our SBS methodology.
- two separate capping steps first with 3' -O-N 3 -dNTPs and then with ddNTPs, are performed. The rationale behind the first capping reaction is to maximize the amount of extension products and to ensure the minimal loss of templates.
- GATCGCGCCGCGCCTTGGCGCGGCGC-3' (SEQ ID No: 4) for ddGTP- N 3 -Cy5; and 5'-GTCAGCGCCGCGCCTTGGCGCGGCGC-S' (SEQ ID No: 5) for ddUTP-N 3 -R6G.
Abstract
Description
Claims
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EP23212547.6A EP4310194A2 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
EP15165262.5A EP2940029B1 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
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US99957607P | 2007-10-19 | 2007-10-19 | |
PCT/US2008/011891 WO2009051807A1 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
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EP23212547.6A Division EP4310194A2 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
EP15165262.5A Division EP2940029B1 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
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EP23212547.6A Pending EP4310194A2 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
EP15165262.5A Active EP2940029B1 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
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EP15165262.5A Active EP2940029B1 (en) | 2007-10-19 | 2008-10-17 | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
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2018
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2021
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Also Published As
Publication number | Publication date |
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US20140093869A1 (en) | 2014-04-03 |
US20170321267A1 (en) | 2017-11-09 |
US20190085388A1 (en) | 2019-03-21 |
EP2207900A4 (en) | 2014-01-15 |
US20220112552A1 (en) | 2022-04-14 |
US11208691B2 (en) | 2021-12-28 |
EP2207900B1 (en) | 2015-04-29 |
US20160090621A1 (en) | 2016-03-31 |
US20110014611A1 (en) | 2011-01-20 |
EP2940029A1 (en) | 2015-11-04 |
EP4310194A2 (en) | 2024-01-24 |
EP2940029B1 (en) | 2023-11-29 |
US10144961B2 (en) | 2018-12-04 |
US9670539B2 (en) | 2017-06-06 |
HK1217106A1 (en) | 2016-12-23 |
US9175342B2 (en) | 2015-11-03 |
WO2009051807A1 (en) | 2009-04-23 |
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